17-8189376-T-G

Position:

• chr17-8189376-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017622.3(BORCS6):​c.765A>C​(p.Pro255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,601,868 control chromosomes in the GnomAD database, including 507,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (42214 hom., cov: 33)
  • Exomes 𝑓: 0.79 (465372 hom.)
• Consequence: BORCS6 NM_017622.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

BORCS6 (HGNC:25939): (BLOC-1 related complex subunit 6) Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.049 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORCS6	NM_017622.3	c.765A>C	p.Pro255=	synonymous_variant	1/1	ENST00000389017.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORCS6	ENST00000389017.6	c.765A>C	p.Pro255=	synonymous_variant	1/1		NM_017622.3	P1
	ENST00000622992.1	n.444T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111438 AN: 152004 Hom.: 42186 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.711

GnomAD3 exomes AF: 0.707 AC: 161089 AN: 227730 Hom.: 61188 AF XY: 0.727 AC XY: 90223 AN XY: 124088

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.796

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.792 AC: 1148315 AN: 1449748 Hom.: 465372 Cov.: 85 AF XY: 0.794 AC XY: 571981 AN XY: 720474

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.858

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.733 AC: 111508 AN: 152120 Hom.: 42214 Cov.: 33 AF XY: 0.730 AC XY: 54263 AN XY: 74370

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.704

Alfa AF: 0.799 Hom.: 70911

Bravo AF: 0.702

Asia WGS AF: 0.573 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8531; hg19: chr17-8092694; COSMIC: COSV66504868; COSMIC: COSV66504868;